Alternative titles; symbols
HGNC Approved Gene Symbol: SEMA5A
Cytogenetic location: 5p15.31 Genomic coordinates (GRCh38): 5:9,035,033-9,546,075 (from NCBI)
Members of the semaphorin protein family, such as SEMA5A, are involved in axonal guidance during neural development (Adams et al., 1996).
Adams et al. (1996) cloned mouse Sema5a, which they designated Semf. The deduced 1,077-amino acid protein contains an N-terminal signal sequence, followed by a semaphorin domain, 7 thrombospondin type-1 repeats (see 188060), a putative transmembrane domain, and a short cytoplasmic tail. It also has 13 conserved cysteines and a conserved N-glycosylation site. Northern blot analysis of whole mouse embryos detected 2 Semf transcripts at embryonic day 10, and their expression decreased toward birth. Semf, Semg (SEMA5B; 609298), Semd (SEMA3A; 603961), and Seme (SEMA3C; 602645) were expressed in specific regions of early mouse embryos, and their expression demarcated distinct compartments of the developing somites or the undifferentiated neuroepithelium. In adult animals, highest Semf expression was detected in muscle, heart, lung, and spleen.
Simmons et al. (1997) identified a partial SEMAF sequence within a YAC covering the cri-du-chat (123450) critical region on chromosome 5. By 5-prime RACE of placenta RNA, Simmons et al. (1998) cloned full-length SEMAF. The deduced 1,074-amino acid protein has a calculated molecular mass of 120 kD. Mouse and human SEMAF proteins have the same domain structure and share 93% amino acid identity. The Sema domain of human SEMAF covers 484 amino acids, the 7 type-1 thrombospondin-like repeats cover about 400 amino acids, and the cytoplasmic tail is 81 amino acids long. Northern blot analysis detected transcripts of 9.6 and 15 kb in all tissues examined. Highest expression was in adult colon, heart, and kidney. Weak expression was detected in fetal brain, lung, and kidney.
Kantor et al. (2004) found that rat Sema5a acted as a bifunctional guidance cue, exerting both attractive and inhibitory effects on developing axons of the fasciculus retroflexus (FR), a diencephalon fiber tract associated with limbic function. The thrombospondin repeats of Sema5a physically interacted with the glycosaminoglycan portion of both chondroitin sulfate proteoglycans (CSPGs) and heparan sulfate proteoglycans (HSPGs). When bound to HSPGs of FR axons, Sema5a behaved as an attractive guidance cue, and when bound to CSPGs of prosomere 2 of the diencephalon, Sema5a behaved as an inhibitory guidance cue. Kantor et al. (2004) concluded that neuronal responses to SEMA5A are dependent on the bound proteoglycan and the biologic context.
Artigiani et al. (2004) showed that mammalian plexin B3 (PLXNB3; 300214) is a high-affinity Sema5a receptor. Plxnb3 was activated by Sema5a, and the Sema5a-Plxnb3 complex triggered intracellular signaling through Met (164860), the receptor for hepatocyte growth factor (142409).
Weiss et al. (2009) demonstrated that expression of SEMA5A is reduced in brains from autistic patients.
Simmons et al. (1998) determined that the SEMA5A gene contains 10 exons and spans more than 200 kb.
By virtue of its inclusion in a YAC contig covering the cri-du-chat critical region, Simmons et al. (1998) mapped the SEMA5A gene to chromosome 5p15.2. They determined that the SEMAF gene covers at least 10% of the cri-du-chat critical region.
By backcross analysis, Simmons et al. (1998) mapped the mouse Sema5a gene to chromosome 15.
For discussion of a possible association between variation in the SEMA5A gene and autism, see 209850.
Adams, R. H., Betz, H., Puschel, A. W. A novel class of murine semaphorins with homology to thrombospondin is differentially expressed during early embryogenesis. Mech. Dev. 57: 33-45, 1996. [PubMed: 8817451] [Full Text: https://doi.org/10.1016/0925-4773(96)00525-4]
Artigiani, S., Conrotto, P., Fazzari, P., Gilestro, G. F., Barberis, D., Giordano, S., Comoglio, P. M., Tamagnone, L. Plexin-B3 is a functional receptor for semaphorin 5A. EMBO Rep. 5: 710-714, 2004. [PubMed: 15218527] [Full Text: https://doi.org/10.1038/sj.embor.7400189]
Kantor, D. B., Chivatakarn, O., Peer, K. L., Oster, S. F., Inatani, M., Hansen, M. J., Flanagan, J. G., Yamaguchi, Y., Sretavan, D. W., Giger, R. J., Kolodkin, A. L. Semaphorin 5A is a bifunctional axon guidance cue regulated by heparan and chondroitin sulfate proteoglycans. Neuron 44: 961-975, 2004. [PubMed: 15603739] [Full Text: https://doi.org/10.1016/j.neuron.2004.12.002]
Simmons, A. D., Overhauser, J., Lovett, M. Isolation of cDNAs from the cri-du-chat critical region by direct screening of a chromosome 5-specific cDNA library. Genome Res. 7: 118-127, 1997. [PubMed: 9049630] [Full Text: https://doi.org/10.1101/gr.7.2.118]
Simmons, A. D., Puschel, A. W., McPherson, J. D., Overhauser, J., Lovett, M. Molecular cloning and mapping of human semaphorin F from the Cir-du-chat candidate interval. Biochem. Biophys. Res. Commun. 242: 685-691, 1998. [PubMed: 9464278] [Full Text: https://doi.org/10.1006/bbrc.1997.8027]
Weiss, L. A., Arking, D. E., Gene Discovery Project of Johns Hopkins & the Autism Consortium. A genome-wide linkage and association scan reveals novel loci for autism. Nature 461: 802-808, 2009. [PubMed: 19812673] [Full Text: https://doi.org/10.1038/nature08490]